QUANTITATIVE ASSESSMENT OF HEPATIC FUNCTION IN CHRONIC HEPATITIS C

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。对某些肝功能和肝血液循环检查的有效性的评价；这是对HALT-C试验的辅助研究。据估计，1998年美国有8,000至10,000名患者死亡，到2010年每年将有30,000名患者死于慢性丙型肝炎（HCV）引起的晚期肝病。丙型肝炎晚期组织学分期、桥接纤维化和肝硬化的患者，出现肝代偿失代偿、需要肝移植、肝癌和肝病死亡的临床证据的风险最大。美国国立卫生研究院对肝纤维化或肝硬化的HCV无应答者试验的假设是，长期使用抗病毒治疗（维持治疗）将减缓肝病的进展。对于有明显纤维化的非肝硬化患者，有效的维持治疗有望减缓或阻止肝硬化的组织学进展。肝硬化患者维持治疗有效反应的标准终点是预防临床代偿失代偿（腹水[腹部积液]、静脉曲张出血[静脉扩张出血]、脑病[脑退行性疾病]），以及通过child - turcot - pugh （CTP）评分临床测量的肝功能稳定。然而，临床终点是疾病进展的不敏感参数。HALT-C治疗是干扰素加利巴韦林的长期治疗。本研究将进行三次测试。首先，在基线，在开始使用HALT-C药物之前，以及在治疗的头六个月后的2年和4年。每个测试周期都是一样的。患者将在CRC住院一天。测试前三天和测试后三天不含咖啡因，并在测试前禁食一晚。唾液样本将在测试后的两天内每天在家收集两次，然后送到CRC。在测试时，将有一个静脉导管放置在手臂上抽血并给予测试化合物。将在三天内收集六份唾液样本。三种化合物静脉给药，三种口服给药。抽血检查肝脏如何清除这些化合物。检查完成后，病人将正常进食。两小时后进行SPECT扫描以测量肝功能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An evaluation of the usefulness of certain tests of the liver function and liver blood circulation; an ancillary study to the HALT-C trial. It is estimated that 8,000 to 10,000 patients in the U.S. died in 1998 and 30,000 will die annually by the year 2010, as a direct result of advanced liver disease from chronic hepatitis C (HCV). Patients with advanced histologic stages of hepatitis C, bridging fibrosis and cirrhosis, are at greatest risk of developing clinical evidence of hepatic decompensation, need for liver transplantation, liver cancer, and death from liver disease. The hypothesis for the National Institutes of Health Trial of HCV nonresponders with fibrosis or cirrhosis is that long-term use of antiviral therapy (maintenance treatment) will slow the progression of liver disease. In noncirrhotic patients who have significant fibrosis, effective maintenance therapy is expected to slow or stop histologic progression to cirrhosis. Standard endpoints for effective response to maintenance therapy in cirrhotic patients are prevention of clinical decompensation, (ascites [the accumulation of fluid in the abdomen], variceal hemorrhage[bleeding from enlarged veins], encephalopathy [degenerative diseases of the brain]), and stabilization of liver function as measured clinically by Childs-Turcott-Pugh (CTP) score. However, clinical endpoints are insensitive parameters of disease progression. HALT-C treatment is long-term therapy with interferon plus ribavirin. Testing will be done three times during this study. First, at baseline, before the beginning of the HALT-C medications, and two and four years after the first six months of treatment. Each testing period will be the same. Patients will be admitted to the CRC for one day. Diets will be caffeine free three days before and three days after the tests and there will be a pre-admit overnight fast. Saliva samples will be collected at home twice a day for two days after testing and then brought to the CRC. At the time of testing , there will be an intravenous catheter placed into the arm to draw blood and administer test compounds. Six saliva samples will be collected over three days. Three compounds will be given by vein and three will be given orally. Blood will be drawn to see how the liver clears these compounds. After the tests are complete, the patient will eat a normal meal. Two hours later a SPECT Scan will be done to allow measurement of hepatic function.